CausalSentinel

Protein Dossier — MAN2B2 (Epididymis-specific alpha-mannosidase)

MR feasibility tier: A — Published pQTL-MR estimates exist for this protein (retrieved below - not computed here).

1. Published MR estimates (retrieved, not computed)

Outcome beta se p method nSNP cis/trans coloc
Non-cancer illness code self-reported: retinal detachment 0.264 0.0972 0.00651 Wald ratio 1 cis NA
Diagnoses - main ICD10: G47 Sleep disorders 0.197 0.0775 0.0109 Wald ratio 1 cis NA
Major depressive disorder 0.159 0.0673 0.0185 Wald ratio 1 cis NA
Non-cancer illness code self-reported: chronic obstructive airways disease or copd 0.228 0.0992 0.0218 Wald ratio 1 cis NA
LDL cholesterol -0.0332 0.015 0.0264 Wald ratio 1 cis NA
Alcohol intake frequency -0.0217 0.0106 0.0413 Wald ratio 1 cis NA
Mean cell volume -0.172 0.0844 0.0418 Wald ratio 1 cis NA
ER-negative Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) -0.0724 0.038 0.0567 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypothyroidism or myxoedema -0.0632 0.0341 0.0634 Wald ratio 1 cis NA
Nucleus accumbens volume 6.05 3.31 0.0679 Wald ratio 1 cis NA
Body fat -0.0275 0.0156 0.0769 Wald ratio 1 cis NA
Diagnoses - main ICD10: K44 Diaphragmatic hernia 0.0907 0.0527 0.0853 Wald ratio 1 cis NA
…and 96 more outcomes (see JSON)              

2. pQTL instrument availability (Tier-B probe)

No prot-* pQTL GWAS dataset found for this protein (matched by UniProt accession and symbol).

3. GWAS Catalog results — traits with signal at this locus

35 association rows across 12 traits (31 genome-wide significant rows). Associations are loci, not causal claims; the mapped gene at a locus is not necessarily the effector gene.

Trait best p lead SNP n assoc study MR status
Epididymis-specific alpha-mannosidase levels 8e-1296 rs2301791 3 GCST90247502 no MR -> candidate analysis
Circulating FUCA1 levels 2e-272 rs4689486 5 GCST90860617 no MR -> candidate analysis
MAN2B2 protein levels 1e-192 rs776707824 16 GCST90469844 no MR -> candidate analysis
Serum levels of protein MAN2B2 2e-62 rs2301793 1 GCST90090583 no MR -> candidate analysis
Cerebrospinal fluid protein MAN2B2 levels 2e-45 rs4689486 1 GCST90944412 no MR -> candidate analysis
Epididymis-specific alpha-mannosidase levels (MAN2B2.9251.28 1e-44 rs2301790 1 GCST90241096 no MR -> candidate analysis
Blood protein levels 6e-44 rs17724993 1 GCST006585 no MR -> candidate analysis
Complement C1q subcomponent subunit C protein levels (SomaSc 1e-36 rs2301791 1 GCST90442570 no MR -> candidate analysis
FUCA1 protein levels 2e-26 rs73209757 3 GCST90469275 no MR -> candidate analysis
Epididymis-specific alpha-mannosidase level in Chronic kidne 1e-13 rs2301791 1 GCST90239270 no MR -> candidate analysis
S-warfarin levels 7e-7 rs115705089 1 GCST90129562 no MR -> candidate analysis
Baseline memory in impaired cognition 9e-7 rs4689486 1 GCST90448422 no MR -> candidate analysis

4. Phenome map — where this gene is a genetic locus, vs. where MR exists

Top diseases by Open Targets association (of 75 total). Associations are loci, not causal claims. The causal-status column is a four-state triage per pair: established (curated) = a curated clinical assertion exists (ClinGen/G2P/GEL/Orphanet/ClinVar — any validity level, MR adds little); exploratory rare-variant signal = ExWAS burden evidence without curation — a candidate NEW gene-disease relationship; common-variant locus = GWAS signal, classic pQTL-MR territory; multi-layer = burden+GWAS together, an allelic-series candidate (the strongest causal setup). Burden estimand is carrier-vs-noncarrier, not per-SD MR.

Disease genetic assoc. burden (ExWAS) causal status MR status
congenital disorder of glycosylation type 1EE with or without immunodeficiency 0.674 established (curated) no MR -> candidate analysis
blood coagulation disease 0.452 common-variant locus no MR -> candidate analysis
placental abruption 0.363 common-variant locus no MR -> candidate analysis
malignant renal pelvis neoplasm 0.363 common-variant locus no MR -> candidate analysis
gastric cancer 0.27 established (curated) no MR -> candidate analysis
congenital disorder of glycosylation 0.182 established (curated) no MR -> candidate analysis

Of the 6 rows above, 6 have no MR estimate in this resource. Across all retrieved diseases for this gene: 0 exploratory rare-variant signal(s), 0 multi-layer (allelic-series candidate) pair(s). Final triage still belongs to a statistical geneticist.

5. Downstream annotation (druggability & safety preview)

Layer Result
ChEMBL druggability 0 known modulators (Epididymis-specific alpha-mannosidase)
gnomAD constraint not available
GWAS Catalog 106 unique SNPs / 192 rows
ClinVar 453 records; 5 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance